This invention relates to the field of formulation chemistry, and more particularly to the formulation of protein materials for subcutaneous injection.
A fluid product intended for subcutaneous injection should have a consistent viscosity and be homogeneous. Freeze dried proteins, such as recombinant bovine somatotropin and growth hormone releasing factor, are amorphous materials of variable and large flake size. The freeze drying process produces material that is not homogeneous. Bovine somatotropin and growth hormone releasing factor have useful biological activity when administered as parenteral injections, but to enable formulation of these materials as homogeneous, easily injectable products having a consistent viscosity, a method is needed for reducing the large amorphous protein flakes to uniform particulates. The size reduction process selected, in addition to being applicable to non-crystaline material, must also be practicable without protein decomposition or loss of potency, without water uptake, and without quantitative loss of material. The process should also lend itself to maintenance of sterile conditions.